Hypoxia, low oxygen tension, has been proposed as a mediator in the local control of blood flow by virtue of its relaxant effect on vascular smooth muscle. Hypoxia may affect vascular smooth muscle indirectly by altering the metabolism of the surrounding or parenchyma tissue causing release of vasoactive substances. Hypoxia may also act directly on vascular smooth muscle to effect relaxation and this direct effect has been observed in isolated vascular smooth muscle. However, the mechanism of this direct effect of oxygen deprivation in vitro is not known and even the relevance of this inhibition to the physiological condition has been questioned. Hypoxia could act at any number of points in the contractile process, from inhibition of muscle stimulation to depression of the chemomechanical transduction process itself. Several of the more probable mechanisms include: 1) changes in intracellular levels of 5'AMP and Pi which inhibit the contractile proteins, 2) release of adenosine, a potent vasodilator, 3) decreases in the Ca++ permeability of the membrane and 4) changes in the membrane potential of the cell membrane. None of these mechanisms have been tested directly and the primary aim of this proposal is to test these possible mechanisms by measuring the various metabolites, membrane permeability to Ca++ and membrane potential of strips subjected to hypoxia. In addition, the interdependence of hypoxia and adenosine will be explored by measuring the changes in the labeled adenosine concentration within strips during different levels of hypoxia. The results of these experiments 1) should shed light on the phenomenon of local control of blood flow, 2) may aid in designing experiments to determine why pulmonary vessels, unlike systemic vessels, constrict in response to hypoxia and, finally, 3) may give some insight into the possible role of hypoxia in atherosclerosis.